Pharmacokinetics and Safety of Single and Multiple Doses of Oral N -Acetylcysteine in Healthy Chinese and Caucasian Volunteers: An Open-Label, Phase I Clinical Study

Alexandros G.Sfakianakis shared this article with you from Inoreader Pharmacokinetics and Safety of Single and Multiple Doses of Oral N -Acetylcysteine in Healthy Chinese and Caucasian Volunteers: An Open-Label, Phase I Clinical Study Μέσω Advances in Therapy Abstract Introduction Few studies have evaluated whether the pharmacokinetics of N-acetyl-cysteine (NAC) are different in Chinese and Caucasian individuals. Methods This single- and multiple-dose, single-centre, open-label, phase I clinical study was conducted in healthy adult volunteers. All participants received oral NAC 600-mg uncoated tablets, which were administered first as a single dose and, following a 48-h wash-out period, twice daily for 3 days. Blood and urine were collected after single- and multiple-dose NAC administration. Adverse event (AE) data were collected throughout the study. Results Fifteen Chinese and 15 Caucasian (mostly Italian) individuals (males 66.7%, mean age 36.8 years) participated in the study. Pharmacokinetic characteristics of NAC were similar in the two cohorts. Following both single- and multiple-dose administration, plasma concentration of NAC increased rapidly, reaching a peak at approximately 1.0 h. Maximum plasma concentration and extent of exposure were higher after multiple doses than after a single dose. The accumulation ratio was relatively consistent in both Chinese (mean ± standard deviation 1.5 ± 0.4) and Caucasian (1.4 ± 0.2) participants. The half-life was 15.4 h in Chinese and 18.7 h in Caucasian participants, and the fraction of NAC excreted in urine in the 36 h following administration was 3.7% in Chinese and 3.8% in Caucasian participants. Two Caucasian participants had a total of 3 AEs (headache, presyncope and dysmenorrhoea). No AEs occurred in Chinese participants. Conclusions The pharmacokinetic characteristics of NAC are similar in healthy Chinese and Caucasian individuals after single and repeated administration. NAC has a favourable tolerability profile. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Expanding the phenotype of MOG antibody-associated disease (MOGAD): half a century of epilepsy and relapsing optic neuritis

Alexandros G.Sfakianakis shared this article with you from Inoreader Expanding the phenotype of MOG antibody-associated disease (MOGAD): half a century of epilepsy and relapsing optic neuritis Μέσω JNNP Online First Autoimmune disease has opened a field for the discovery of new phenotypes in clinical neurology. The unravelling of the autoimmune pathophysiology has led to successful novel treatment strategies including long-term immune suppression.1 In myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), damage to the central nervous system is attack related.2 The clinical phenotype of MOGAD is heterogenous and expanding. Here we illustrate a new phenomenon in a MOGAD-seropositive patient whom we have followed-up for 48 years: the synchronisation of relapsing, steroid responsive epilepsy and optic neuritis (ON). The long-term follow-up with repeated imaging, electrodiagnostic and laboratory tests of blood and cerebrospinal fluid permits to exclude with confidence that this phenotype is due to the more commonly described association of seizure activity with ON in acute encephalitis.3 The 69-year-old woman with relapsing ON reports the attacks to be often preceded by a cluster of seizures. Forty-eight years ago,... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prevalence, predictors and prognosis of incidental intracranial aneurysms in patients with suspected TIA and minor stroke: a population-based study and systematic review

Alexandros G.Sfakianakis shared this article with you from Inoreader Prevalence, predictors and prognosis of incidental intracranial aneurysms in patients with suspected TIA and minor stroke: a population-based study and systematic review Μέσω JNNP Online First Introduction Unruptured intracranial aneurysms (UIAs) are common incidental imaging findings, but there are few data in patients with transient ischaemic attack (TIA)/stroke. The frequency of UIA might be higher due to shared risk factors, but rupture risk might be reduced by intensive secondary prevention. We determined the prevalence and prognosis of UIA in patients with suspected TIA/minor stroke. Methods All patients referred to the population-based Oxford Vascular Study (2011–2020) with suspected TIA/minor stroke and non-invasive angiography were included. We determined the prevalence of incidental asymptomatic UIA and the risk of subsequent subarachnoid haemorrhage (SAH) by follow-up on intensive medical treatment, with guideline-based monitoring/management. We also did a systematic review of UIA prevalence/prognosis in cohorts with TIA/stroke. Findings Among 2013 eligible patients, 95 (4.7%) had 103 previously unknown asymptomatic UIA. Female sex (OR 2.3, 95% CI 1.5 to 3.7), smoking (2.1, 1.2 to 3.6) and hypertension (1.6, 1.0 to 2.5) were independently predictive of UIA, with a prevalence of 11.1% in those with all three risk factors. During mean follow-up of 4.5 years, only one SAH occurred: 2.3 (95% CI 0.3 to 16.6) per 1000 person-years. We identified 19 studies of UIA in TIA/stroke cohorts (n=12 781), all with either symptomatic carotid stenosis or major acute stroke. The pooled mean UIA prevalence in patients with TIA/stroke was 5.1% (95% CI 4.8 to 5.5) and the incidence of SAH was 4.6 (95% CI 1.9 to 11.0) per 1000 person-years. Interpretation The 5% prevalence of UIA in patients with confirmed TIA/minor stroke is likely higher than that in the general population. However, the risk of SAH on intensive medical treatment and guideline-based management/monitoring is low. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Associations of APOE e2 genotype with cerebrovascular pathology

Alexandros G.Sfakianakis shared this article with you from Inoreader Associations of APOE e2 genotype with cerebrovascular pathology: a postmortem study of 1275 brains Μέσω JNNP Online First Objective We assessed the association of apolipoprotein E (APOE) genotype with cerebrovascular disease (CVD) in a large neuropathological database maintained by the National Alzheimer's Coordinating Center (NACC). Such a comprehensive investigation of APOE and CVD pathology has not heretofore been conducted. We focused on APOE e2, an established neuroprotective genetic variant against Alzheimer's disease. M ethods To implement these objectives APOE associations in the NACC database of 1275 brains with 11 CVD pathologies, including old and recent infarcts, haemorrhages, cerebral amyloid angiopathy (CAA) and arteriosclerosis, were examined. These pathologies were uniformly and semiquantitatively measured across 39 Alzheimer's Disease Center sites. We used 2 statistics and ordinal regression to assess the significance of associations and Bonferroni corrected for multiple comparisons. Results Of the cases, 98 were e2/e3 or e2/e2 genotypes ('e2' carriers), 621 were e3 homozygotes ('e3' group), and 556 were e4/e3 (442) or e4/e4 (114) genotypes ('e4' group). Results indicated that the APOE e4 allele significantly increased risk for CAA. After stratification by CAA presence/absence, we found that in those cases in which CAA was present, APOE e2 significantly increased risk for gross haemorrhage. All other associations were negative. Conclusions In this, the largest st udy of APOE e2 effects on pathologically verified CVD, e2 was not protective against any CVD pathology compared with e3 homozygotes, including CAA. Regarding the latter pathology, e4 was associated with increases in its severity. Furthermore, and perhaps unexpectedly, e2 significantly increased risk of acute/subacute gross haemorrhage in the presence of CAA. Thus, there were limits to e2 neuroprotection against amyloidosis, despite its known and large protective effects against diffuse and neuritic amyloid plaques compared with e3/e3 and e4 carriers in this very collection. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The future of neuroprotection in stroke

Alexandros G.Sfakianakis shared this article with you from Inoreader The future of neuroprotection in stroke Μέσω JNNP Online First Investigators acknowledge the limitations of rodent or non-human primate stroke models, hundreds of putative neuroprotectants have been evaluated in preclinical models, but not one has entered the clinical realm. Initial studies focused on the neuron, but in recent years the focus has widened to also include other neural cells including astrocytes, pericytes and endothelial cells, which together form the neurovas cular unit. Some new developments raise renewed hope for neuroprotection: the appearance of new compounds with multiple mechanisms of action, or the promulgation of new standards for a rigorous preclinical testing. At the bedside in the last 5 years, uric acid and nerinetide are the only compounds tested for clinical efficacy in randomised controlled trials (RCTs), where all patients had to receive reperfusion therapies, either intravenous thrombolysis and/or mechanical thrombectomy. In addition, otaplimastat, 3K3A-activated protein C (APC), intra-arterial verapamil and intra-arterial hypothermia were also assessed in combination with reperfusion therapy, but in RCTs that only included feasibility or safety outcomes. Some of these compounds yielded promising results which are discussed in this review. Altogether, a deeper knowledge of the mechanisms involved in the ischaemic death process at the neurovascular unit, an improved preselection and evaluation of drugs at the preclinical stage and the testing of putative neuroprotectants in enriched clinical studies of patients receiving reperfusion therapies, might prove more effective than in the past to reverse a dismal situation that has lasted already too long. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Intraventricular neuroepithelial tumors: surgical outcome, technical considerations and review of literature

Alexandros G.Sfakianakis shared this article with you from Inoreader Intraventricular neuroepithelial tumors: surgical outcome, technical considerations and review of literature Μέσω BMC Cancer - Latest Articles Intraventricular neuroepithelial tumors (IVT) are rare lesions and comprise different pathological entities such as ependymomas, subependymomas and central neurocytomas. The treatment of choice is neurosurgica... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

High proportion of anergic B cells in the bone marrow defined phenotypically by CD21(−/low)/CD38- expression predicts poor survival in diffuse large B cell lymphoma

Alexandros G.Sfakianakis shared this article with you from Inoreader High proportion of anergic B cells in the bone marrow defined phenotypically by CD21(−/low)/CD38- expression predicts poor survival in diffuse large B cell lymphoma Μέσω BMC Cancer - Latest Articles Diffuse large B cell lymphoma (DLBCL) is the commonest lymphoma that is highly aggressive where one-third of the patients relapse despite effective treatment. Interaction between the lymphoma cells and the non... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Too much serotonin causes signs and symptoms that can range from mild (shivering and diarrhea) to severe (muscle rigidity, fever and seizures).

Alexandros G.Sfakianakis shared this article with you from Inoreader Serotonin Syndrome Associated With Vilazodone Overdose in a 22-Month-Old Treated With Dexmedetomidine Μέσω ScienceDirect Publication: The Journal of Emergency Medicine Publication date: Available online 4 November 2020 Source: The Journal of Emergency Medicine Author(s): Erica Schlichting, Chris Welter, Tammi Schaeffer, Tania D. Strout View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Serotonin Syndrome Associated With Vilazodone Overdose in a 22-Month-Old Treated With Dexmedetomidine

Alexandros G.Sfakianakis shared this article with you from Inoreader Serotonin Syndrome Associated With Vilazodone Overdose in a 22-Month-Old Treated With Dexmedetomidine Μέσω ScienceDirect Publication: The Journal of Emergency Medicine Publication date: Available online 4 November 2020 Source: The Journal of Emergency Medicine Author(s): Erica Schlichting, Chris Welter, Tammi Schaeffer, Tania D. Strout View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Self-reported health without clinically measurable benefits among adult users of multivitamin and multimineral supplements: a cross-sectional study

Alexandros G.Sfakianakis shared this article with you from Inoreader Self-reported health without clinically measurable benefits among adult users of multivitamin and multimineral supplements: a cross-sectional study Μέσω BMJ Open Current Issue Objective Multiple clinical trials fail to identify clinically measurable health benefits of daily multivitamin and multimineral (MVM) consumption in the general adult population. Understanding the determinants of widespread use of MVMs may guide efforts to better educate the public about effective nutritional practices. The objective of this study was to compare self-reported and clinically measurable health outcomes among MVM users and non-users in a large, nationally representative adult civilian non-institutionalised population in the USA surveyed on the use of complementary health practices. Design Cross-sectional analysis of the effect of MVM consumption on self-reported overall health and clinically measurable health outcomes. Participants Adult MVM users and non-users from the 2012 National Health Interview Survey (n=21 603). Primary and secondary outcome measures Five psychological, physical, and functional health outcomes: (1) self-rated health status, (2) needing help with routine needs, (3) history of 10 chronic diseases, (4) presence of 19 health conditions in the past 12 months, and (5) Kessler 6-Item (K6) Psychological Distress Scale to measure non-specific psychological distress in the past month. Results Among 4933 adult MVM users and 16 670 adult non-users, MVM users self-reported 30% better overall health than non-users (adjusted OR 1.31; 95% CI 1.17 to 1.46; false discovery rate adjusted p<0.001). There were no differences between MVM users and non-users in history of 10 chronic diseases, number of present health conditions, severity of current psychological distress on the K6 Scale and rates of needing help with daily activities. No effect modification was observed after stratification by sex, education, and race. Conclusions MVM users self-reported better overall health despite no apparent differences in clinically measurable health outcomes. These results suggest that widespread use of multivitamins in adults may be a result of individuals' positive expectation that multivitamin use leads to better health outcomes or a self-selection bias in which MVM users intrinsically harbour more positive views regarding their health. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

ZMYND8 expression in breast cancer cells blocks T-lymphocyte surveillance to promote tumor growth

Alexandros G.Sfakianakis shared this article with you from Inoreader ZMYND8 expression in breast cancer cells blocks T-lymphocyte surveillance to promote tumor growth Μέσω Cancer Research Online First Articles Emerging studies indicate that DNA damage in cancer cells triggers antitumor immunity, but its intrinsic regulatory mechanism in breast cancer cells remains poorly understood. Here, we show that ZMYND8 is upregulated and inhibits micronucleus formation and DNA damage in breast cancer cells. Loss of ZMYND8 triggered activation of the DNA sensor cyclic guanosine monophosphate-adenosine monophosphate synthase in micronuclei, leading to further activation of the downstream signaling effectors stimulator of interferon genes and NF-kappaB, but not TANK-binding kinase 1 and interferon regulatory factor 3, thereby inducing the expression of interferon-beta and interferon-stimulated genes (ISGs) in breast cancer cells in vitro and tumors in vivo. ZMYND8 knockout (KO) in breast cancer cells promoted infiltration of CD4+ and CD8+ T cells leading to tumor inhibition in syngeneic mouse models, which was significantly attenuated by treatment of anti-CD4/CD8 depleting antibodies or anti-IFNAR 1 antibody and in immunodeficient Rag1 KO mice. In human breast tumors, ZMYND8 was negatively correlated with ISGs, CD4, CD8A, CD8B, and the tumor-lymphocyte infiltration phenotype. Collectively, these findings demonstrate that maintenance of genome stability by ZMYND8 causes breast cancer cells to evade cytotoxic T-lymphocyte surveillance which leads to tumor growth. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The microbiome and cancer: creating friendly neighborhoods and removing the foes within

Alexandros G.Sfakianakis shared this article with you from Inoreader The microbiome and cancer: creating friendly neighborhoods and removing the foes within Μέσω Cancer Research Online First Articles The human body is colonized by the microbial cells that are estimated to be as abundant as human cells, yet their genome is roughly 100 times the human genome, providing significantly more genetic diversity. The past decade has observed an explosion of interest in examining the existence of microbiota in the human body and understanding its role in various diseases including inflammatory bowel disease, neurologic diseases, cardiovascular disorders, and cancer. Many studies have demonstrated differential community composition between normal tissue and cancerous tissue, paving the way for investigations focused on deciphering the cause-and-effect relationships between specific microbes and initiation and progression of various cancers. Also, evolving are the strategies to alter tumor-associated dysbiosis and move it towards eubiosis with holistic approaches to change the entire neighborhood or to neutralize pathogenic strains. In this review, we discuss important pathogenic bacte ria and the underlying mechanisms by which they impact cancer progression. We summarize key microbiota alterations observed in multiple tumor niches, their association with clinical stages, and their potential use in cancer diagnosis and management. Finally, we discuss microbiota-based therapeutic approaches. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.